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FettsuchtFettsucht
Lajos Lajos SzollárSzollárSemmelweis Semmelweis Universität Universität
Fakultät für MedizinFakultät für MedizinInstitut für PathophysiologieInstitut für Pathophysiologie
20020066
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ObesityObesity
Definition of obesity: Increase of adipose tissueDefinition of obesity: Increase of adipose tissue Criteria of obesity, grade of severityCriteria of obesity, grade of severity
Broca-index, relatíve weight, ideal weight, body mass indexBroca-index, relatíve weight, ideal weight, body mass index
Frequency, geographical distribution, time-trendsFrequency, geographical distribution, time-trends Effects on mortality and morbidityEffects on mortality and morbidity Consequences and complicationsConsequences and complications Classification of obesityClassification of obesity
Hypertrophic-hyperplasticHypertrophic-hyperplastic Central-peripheralCentral-peripheral
Pathogenesis of obesityPathogenesis of obesity
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Body fat in obesityBody fat in obesity
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ENERGY RESERVES IN LEAN AND OBESE ENERGY RESERVES IN LEAN AND OBESE SUBJECTSSUBJECTS
((After After BrayBray,, 1976 1976 ))
Body weight 70 100 Fat (triglyceride) 15 564.840 40 1.506.240Proteine (muscle) 6 100.416 7 117.152Glycogen 0.07 1.170 0.07 1.170
kg kJ kg kJ
Lean Obese
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ObesityObesity
Definition of obesity: Increase of adipose tissueDefinition of obesity: Increase of adipose tissue Criteria of obesity, grade of severityCriteria of obesity, grade of severity
Broca-index, relatíve weight, ideal weight, body mass indexBroca-index, relatíve weight, ideal weight, body mass index
Frequency, geographical distribution, time-trendsFrequency, geographical distribution, time-trends Effects on mortality and morbidityEffects on mortality and morbidity Consequences and complicationsConsequences and complications Classification of obesityClassification of obesity
Hypertrophic-hyperplasticHypertrophic-hyperplastic Central-peripheralCentral-peripheral
Pathogenesis of obesityPathogenesis of obesity
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Clinically useful anthropometric Clinically useful anthropometric methodsmethods
Broca-index: ideal weight=body height (cm)-100Broca-index: ideal weight=body height (cm)-100
Modified Broca-index: ideal weight=((body height (cm)-100))-10 %Modified Broca-index: ideal weight=((body height (cm)-100))-10 %
Relatíve weight: actual weight / ideal weight x 100 obese > 120Relatíve weight: actual weight / ideal weight x 100 obese > 120
BMI (BMI (BBody ody MMass ass IIndex), Quetelet-index:ndex), Quetelet-index:
body weight (kg) / body heightbody weight (kg) / body height2 2 (m(m22))
desirable < 25, overweight 27-30, obese >30desirable < 25, overweight 27-30, obese >30
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BMI (body mass BMI (body mass index)index)
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CLASSIFICATIONBMI (kg/m²) Risk of comorbidities
Underweight <18.5 Low (but risk of other clinical problems increased)
Normal range 18.5-24.9 Average
Overweight >25
Pre-obese 25.0-29.9 Increased
Obese class I 30.0-34.9 Moderate
Obese Class II 35.0-39.9 Severe
Obese Class III >40.0 Very severe
Classification of overweight in adults according to
BMI. Obesity is classified as BMI >30 kg/m²
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ObesityObesity
Definition of obesity: Increase of adipose tissueDefinition of obesity: Increase of adipose tissue Criteria of obesity, grade of severityCriteria of obesity, grade of severity
Broca-index, relatíve weight, ideal weight, body mass indexBroca-index, relatíve weight, ideal weight, body mass index
Frequency, geographical distribution, time-trendsFrequency, geographical distribution, time-trends Effects on mortality and morbidityEffects on mortality and morbidity Consequences and complicationsConsequences and complications Classification of obesityClassification of obesity
Hypertrophic-hyperplasticHypertrophic-hyperplastic Central-peripheralCentral-peripheral
Pathogenesis of obesityPathogenesis of obesity
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Prevalence of Overweight in Girls and Boys by Race Prevalence of Overweight in Girls and Boys by Race and Ageand Age
11.5 11.29.2
11.6
22.219.6
12.4
26.6
19.4
0
5
10
15
20
25
30
White Black Mexican American
Prev
alen
ce %
Ages 2-5 Ages 6-11 Ages 12-19
Ogden CL, et al. JAMA 2002;288:1730
8.85.9
1312
17.1
27.3
12.8
20.7
27.5
0
5
10
15
20
25
30
White Black Mexican American
Pre
vale
nce
%Ages 2-5 Ages 6-11 Ages 12-19
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W.Samoa (urban)
Kuwait
East Germany
USA
Saudi Arabia
W. Germany
Czech Republic
England
Canada
Netherlands
Australia
Brazil
Japan
China
Women Men
80 70 60 50 40 30 20 10 0 10 20 30 40 50 60 70 80
% population
Age rangeYear *
* Most recent available data. Surveys conducted between 1988 and 1994.
25-6918+
25-6420-74
15+25-6920-6516-6418-7420-5920-6915-6425-64
20+20-45
GLOBAL PREVALENCE OF OBESITY (defined as BMI >30)
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Total Prevalence of Obesity in the U.S.: Total Prevalence of Obesity in the U.S.: Men and Women (Ages 20-74 years)Men and Women (Ages 20-74 years)
10.712.1 12.7
20.6
27.7
15.8 16.6 17
25.9
34
0
5
10
15
20
25
30
35
40
1960-62 1971-74 1976-80 1988-94 1999-00
Men
Women
Pre
vale
nce
%
Flegal KM, et al. JAMA 2002;288:1724
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1978 19910
10
20
30
40
50
60
70
80
Pre
va
len
ce
of
ob
esit
y (
%)
W. Samoa (Urban)
25-69 yrs
1978 19910
10
20
30
40
50
60
70
80
Pre
va
len
ce o
f o
besit
y (
%)
19821987
1993 19751989 1980
1986/871991
1995 19731978
1991 19851989
19920
10
20
YEAR
Pre
vale
nc
e o
f o
bes
ity
(%)
19821987
1993 19751989 1980
1986/871991
1995 19731978
1991 19851989
19920
10
20
YEAR
Pre
vale
nce o
f o
besit
y (%
)THE GROWING EPIDEMIC OF OBESITY
Women
Japan20+ yrs.
Brazil 25-64 yrs.
England16-64 yrs.
USA20-74 yrs.
Former E. Germany25-65 yrs.
Men
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Historic, current and projected obesity prevalence rates (BMI > 30)
Kopelman, Nature 404:635, 2000
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ObesityObesity
Definition of obesity: Increase of adipose tissueDefinition of obesity: Increase of adipose tissue Criteria of obesity, grade of severityCriteria of obesity, grade of severity
Broca-index, relatíve weight, ideal weight, body mass indexBroca-index, relatíve weight, ideal weight, body mass index
Frequency, geographical distribution, time-trendsFrequency, geographical distribution, time-trends Effects on mortality and morbidityEffects on mortality and morbidity Consequences and complicationsConsequences and complications Classification of obesityClassification of obesity
Hypertrophic-hyperplasticHypertrophic-hyperplastic Central-peripheralCentral-peripheral
Pathogenesis of obesityPathogenesis of obesity
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BMI and mortalityBMI and mortality
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ObesityObesity
Definition of obesity: Increase of adipose tissueDefinition of obesity: Increase of adipose tissue Criteria of obesity, grade of severityCriteria of obesity, grade of severity
Broca-index, relatíve weight, ideal weight, body mass indexBroca-index, relatíve weight, ideal weight, body mass index
Frequency, geographical distribution, time-trendsFrequency, geographical distribution, time-trends Effects on mortality and morbidityEffects on mortality and morbidity Consequences and complicationsConsequences and complications Classification of obesityClassification of obesity
Hypertrophic-hyperplasticHypertrophic-hyperplastic Central-peripheralCentral-peripheral
Pathogenesis of obesityPathogenesis of obesity
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Mortality in obesityMortality in obesity
CauseNon- obese
mortality=100
Men Women
Diabetes mellitus 383 372Gallstones 206 284Post surgery 200 300Cardiovascular and kidney 149 177Accidents 111 135Malignant diseases 97 100Suicide 79 73Tuberculosis 21 35
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Health Consequences of Obesity
• Cardiovascular disease
• Dyslipidemia
• Type II diabetes mellitus
• Hypertension
• Cancer, some common types
• Degenerative joint disease
• Gallstones
• Gynecologic irregularities
• Sleep apnea syndrome
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Data from British Regional Heart Survey.
18 20 22 24 26 28 30 32 341.0
1.2
1.4
1.6
1.8
2.0
2.2
2.4
2.6
2.8
6.6
6.2
5.8
Total cholesterol
Triglycerides
HDL cholesterol
Body Mass Index (kg/m²)
0
10
20
30
40
50
60
SBP
Obesity: cardiovascular risk
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26 -Year Incidence/10,000 of Coronary Heart Disease in Women and Men by BMI26 -Year Incidence/10,000 of Coronary Heart Disease in Women and Men by BMI
76119
179223
268292
0
100
200
300
400
500
<25 25-<30 30+
<50 years 50+ years
BMI Levels
Hubert HB et al. Circulation 1983;67:968-977.
177
255
350333366
440
0
100
200
300
400
500
600
<25 25-<30 30+
<50 years 50+ years
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BMI and relative risk (a=woman
b=men)Kopelman,
Nature 404:635, 2000
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DCEM/2001DCEM/2001
OBESITY
volumeoverload
pressureoverload
ARTERIALHYPERTENSION
sympatheticactivity
vascularhypertrophy
Na+
retention
peripheralinsulin-resistance
abdominal fat
insulin secretion
release of Free Fatty Acids
type 2diabetes
dyslipidemiahyperinsulinemiahyperinsulinemia
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Type 2Type 2 diabetes and obesity diabetes and obesity
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The risk of diabetes in relation to weight and weight change.
BMI at 21 years
Weight change since age 21
0
5
10
15
20
25
<5 kg 5-10 kg 11+ kg
<22
22-23
24+
1.0
1.0
2.1
2.5
3.6
5.3
6.3
9.1
21.1
From: Chan et al. 1994, Diabetes Care, 17: 961.
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Osteoarthrosis and obesityOsteoarthrosis and obesity
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Infertility and obesityInfertility and obesity
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Gout and Gout and obesityobesity
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Obesity and ovarian cancerObesity and ovarian cancer
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Consequences of obesityConsequences of obesity
CardiovascularCardiovascular system system
ArteriosclerosisArteriosclerosis
CongestCongestíív v heart failure, cheart failure, cor pulmonor pulmonaleale
VVenous disordersenous disorders, thrombophlebitis, thrombophlebitis
HHyypertenpertensionsion
Diabetes mellitusDiabetes mellitus
AlAlveolveolarar h hyypoventilpoventilationation (Pickwick-s(Pickwick-syndromeyndrome))
Gastrointestinal disorders Gastrointestinal disorders (fatty liver,gallstones)(fatty liver,gallstones)
KidneyKidney
AArthrosisrthrosis
EndoEndocrine system crine system (reproductive and menstrual disorders,(reproductive and menstrual disorders, toxaemia toxaemia))
Other Other (i(intertrigosusntertrigosus dermatosisdermatosis, hiatus hernia, e, hiatus hernia, endometrindometrial al carcinomacarcinoma))
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Diabetes
Gall bladder disease
Hypertension
Dyslipidaemia
Insulin resistance
Breathlessness
Sleep apnoea
Greatly increased(relative risk >>3)
Coronary heart disease
Osteoarthritis (knees)
Hyperuricaemia and gout
Moderately increased(relative risk
ca 2-3)
Cancer (breast cancer in postmenopausal women, endometrial cancer, colon cancer)
Reproductive hormone abnormalities
Polycystic ovary syndrome
Impaired fertility
Low back pain
Increased anaesthetic risk
Foetal defects arising from maternal obesity
Slightly increased(relative risk
ca 1-2)
Relative risk of health problems associated with
obesity in developed countries.
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ObesityObesity
Definition of obesity: Increase of adipose tissueDefinition of obesity: Increase of adipose tissue Criteria of obesity, grade of severityCriteria of obesity, grade of severity
Broca-index, relatíve weight, ideal weight, body mass indexBroca-index, relatíve weight, ideal weight, body mass index
Frequency, geographical distribution, time-trendsFrequency, geographical distribution, time-trends Effects on mortality and morbidityEffects on mortality and morbidity Consequences and complicationsConsequences and complications Classification of obesityClassification of obesity
Hypertrophic-hyperplasticHypertrophic-hyperplastic Central-peripheralCentral-peripheral
Pathogenesis of obesityPathogenesis of obesity
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Increased Substantially increased
Men >94 cm (37 inches) >102 cm (40 inches)
Women >80 cm (32 inches) >88 cm (35 inches)
Sex-specific waist circumferences that denote "increased risk" and "substantially increased risk" of metabolic
complications associated with obesity in Caucasians.
Risk of obesity associated metabolic complications
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Assessment of accumulation of abdominal fatby measurement of waist at mid-distance between bottom of rib cage and iliac crest. Amount of visceral adipose tissue that can be assessed by CT canbe estimated by waist measurementDespres et al. BMJ 322:716,2001
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The Metabolic Syndrome andThe Metabolic Syndrome andAssociated CVD Risk FactorsAssociated CVD Risk Factors
Insulin Resistance
AtherosclerosisAtherosclerosis
Endothelial Dysfunction
Hypertension
Abdominal obesity
Hyperinsulinaemia
Dyslipidaemia• high TGs
• small dense LDL• low HDL-C
Diabetes
Hypercoagulability
Deedwania PC. Am J Med 1998;105(1A);1S-3S.
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HBP Inflam-mation Insulin Diabetes TG
Dense LDL-C
Low HDL-C Coag.
Interrelationships Between Insulin Resistance and Interrelationships Between Insulin Resistance and AtherosclerosisAtherosclerosis
Insulin Resistance
Endothelial dysfunction
Atherosclerosis
Obesity
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ObesityObesity
Definition of obesity: Increase of adipose tissueDefinition of obesity: Increase of adipose tissue Criteria of obesity, grade of severityCriteria of obesity, grade of severity
Broca-index, relatíve weight, ideal weight, body mass indexBroca-index, relatíve weight, ideal weight, body mass index
Frequency, geographical distribution, time-trendsFrequency, geographical distribution, time-trends Effects on mortality and morbidityEffects on mortality and morbidity Consequences and complicationsConsequences and complications Classification of obesityClassification of obesity
Hypertrophic-hyperplasticHypertrophic-hyperplastic Central-peripheralCentral-peripheral
Pathogenesis of obesityPathogenesis of obesity
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Pathogenesis of ObesityPathogenesis of Obesity „„Pure” OvereatingPure” Overeating Disturbances in Appetite RegulationDisturbances in Appetite Regulation Disturbances in Intermediate MetabolismDisturbances in Intermediate Metabolism Defective Thermogenesis Defective Thermogenesis „„Thrifty” Gen ExpressionThrifty” Gen Expression
Treatments AvailableTreatments Available
DietDiet DrugDrug SurgerySurgery
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Energy intake and demand in developped countries in Energy intake and demand in developped countries in the XX. Centurythe XX. Century
2800
2900
3000
3100
3200
3300
3400
1882 1925 1950 1970
Energy intake
Energia demand
kcal
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Prevalence of overweight and intake of fatPrevalence of overweight and intake of fat
U.S.A.
India
Cuba
AustrailaBrazil
Malaysia
China
Kyrgyzstan
Mauritius
Phillipines
Saudi Arabia
S. Africa
Tunisia
CongoMali
Russian Fed
Italy
Morocco
Kuwait
New Caledonia
0
10
20
30
40
50
60
70
80
15 20 25 30 35 40
Percentage of energy from fat
Pe
rce
nt
ov
erw
eig
ht
actual obesity predicted obesity
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Ludwig
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Energy intake and demand in developped countries in Energy intake and demand in developped countries in the XX. Centurythe XX. Century
2800
2900
3000
3100
3200
3300
3400
1882 1925 1950 1970
Energy intake
Energia demand
kcal
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Obesity and lifestyleObesity and lifestyle
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Percent of Adults Physically InactivePercent of Adults Physically Inactive
0
10
20
30
40
50
60
70
Women Men
18-2425-4445-6465-7475+
Age-Groups
Percent
Source—Advance Data from Vital and Health Statistics. #325, April 7, 2002
Ages 45-54 Ages 55-Ages 45-54 Ages 55-6464
Percent of Adults Percent of Adults with Diabeteswith Diabetes
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Pathogenesis of ObesityPathogenesis of Obesity „„Pure” OvereatingPure” Overeating Disturbances in Appetite RegulationDisturbances in Appetite Regulation Imbalance in Energy ExpenditureImbalance in Energy Expenditure Defective Thermogenesis Defective Thermogenesis „„Thrifty” Gen ExpressionThrifty” Gen Expression
Treatments AvailableTreatments Available
DietDiet DrugDrug SurgerySurgery
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Hypothalamic areas implicated in eating behaviour
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Pathogenesis of ObesityPathogenesis of Obesity „„Pure” OvereatingPure” Overeating Disturbances in Appetite RegulationDisturbances in Appetite Regulation Imbalance in Energy ExpenditureImbalance in Energy Expenditure Defective Thermogenesis Defective Thermogenesis „„Thrifty” Gen ExpressionThrifty” Gen Expression
Treatments AvailableTreatments Available
DietDiet DrugDrug SurgerySurgery
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„Thrifty” gen and obesity
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Genes and environment in type 2 diabetesGenes and environment in type 2 diabetesand atherosclerosisand atherosclerosis
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Pima IndiansPima Indians T Thrifty geneshrifty genes
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Thermogenesis in menThermogenesis in men
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Pathogenesis of ObesityPathogenesis of Obesity „„Pure” OvereatingPure” Overeating Disturbances in Appetite RegulationDisturbances in Appetite Regulation Imbalance in Energy ExpenditureImbalance in Energy Expenditure Defective Thermogenesis Defective Thermogenesis „„Thrifty” Gen ExpressionThrifty” Gen Expression LeptinLeptin
Treatments AvailableTreatments Available
DietDiet DrugDrug SurgerySurgery
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Monogenic obesity in rodentsMonogenic obesity in rodents
SpontaneousSpontaneous Lack of leptin (ob/ob)Lack of leptin (ob/ob) Leptin receptor defect Leptin receptor defect
(db/db)(db/db) Ectopic Agouti expressio Ectopic Agouti expressio
(Ay)(Ay) „„Fat rich” (fa/fa)Fat rich” (fa/fa)
Genetically manipulatedGenetically manipulated Serotonin 2C-receptor KOSerotonin 2C-receptor KO Melanocortin-4 receptor KOMelanocortin-4 receptor KO Agouti related protein (AgRP) Agouti related protein (AgRP)
hyperexpressiohyperexpressio Neuropeptid Y (NPY) receptor KONeuropeptid Y (NPY) receptor KO CRH hyperexpessionCRH hyperexpession Bombesin B-3 receptor KOBombesin B-3 receptor KO Glut-4 hyperexpressionGlut-4 hyperexpression
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The ob/ob mouse and its normal counterpart
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Serum leptin and body fat
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Soluble leptin receptors, immunoreactive leptin and BMIShimizu et al., Nutrition 18:309 (2002)
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Hypothetical risk of obesityHypothetical risk of obesityHill et al., Science 280:1371 (1998)Hill et al., Science 280:1371 (1998)
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A systematic approach to management based on BMI and other risk factors
Assess overall health risk from BMI and other risk factors, e.g. waist circumference
MANAGEMENT STRATEGIES
OVERALL HEALTH RISK
NO
Additional risk factors ?
YES
BMI
Refer to specialist for separate management and consideration of surgery if conventional treatment fails. Aim for 20-30% weight reduction.
Use ful therapy including drugs to achieve >10% weight loss.
Goal for diet, exercise, behaviour: primarily geared to risk management. Weight loss needed if risk not reduced substantially within 3 months, then aim for 5-10 kg over 24 weeks by mild energy deficit. If not achieving this weight reduction at 24 weeks and risks persist, test usefulness of drug to reduce risk by weight management.
Weight maintenance, healthy diet, exercise.
Elevated waist circumference: institute weight management.Family history of obesity: prevent weight gain >3 kg.Smoking: stop with dietary advice.Lipids high: dietary advice.Hypertensive: diet, exercise, weight maintenance.Glucose intolerance: exercise, diet, weight maintenance.
Healthy diet and advice on preventing weight gain.
Goal of 5-10% weight loss without risk appropriate.
Consider very low calorie diet and drug therapy if diet, exercise and lifestyle programme unsuccessful after 12 weeks in reducing all risk factors.
Average
Increased
Moderate
Severe
Verysevere
Very severe
Moderate
Severe
Increased
BMI18.5 -24.9
BMI>40
BMI25 - 29.9
BMI30 - 34.9
BMI35 - 39.9
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